The proposed research is an interdisciplinary, interdepartmental collaborative effort to enable us to explore the changes in functional activity in the human brain which occur in response to various physiologic stimuli in the normal state and in pathologic conditions. The rationale behind the approach to this work is the fact that regional functional activity, metabolism and blood flow in the brain are closely linked normally. When a region of the brain increases, there is then a subsequent increase in local blood flow. Thus, by mapping the changes in local cerebral blood flow that occur in various physiologic and pathophysiologic conditions it might be possible to infer something about the functional activity in that region. The physiologic stimuli that will be investigated are: visual, auditory, somatosensory and cognitive (verbal and spatial). In addition to these studies, the alterations in cerebral blood flow that occur in various disease processes will be explored. The regional hemodynamic alterations in patients with Alzheimer's disease and their response to cognitive stimuli will be investigated and compared to normal control subjects. Similarly, the alterations in regional cerebral blood flow in patients with acute strokes and transient ischemic attacks during cognitive activity will be studied. In patients with schizophrenia and affective disorders the response of the cerebral circulation to cognitive stimulation will be investigated. The relationship of these changes to measures of psychopathology and neuropsychological functioning will be examined. The nature of regional cerebral blood flow abnormalities in patients with seizure disorders will also be examined. The hemodynamic alterations that are present in the epileptic foci and in the mirror foci and their response to medical and/or surgical control of the seizures will be studied. The sensitivity of cerebral blood flow to alterations in arterial CO2 levels will be determined in normal subjects.